Ischemic and reperfusion injury are major causes of disability and death in the United States. Ischemia is caused by a blockage and cessation of blood flow to a region of tissue, and may occur in multiple tissues, including the heart in diseases such as myocardial infarction and the brain, such as in ischemic stroke. Reperfusion injury may occur following recanalization of an occluded vessel, and reflow of blood into an ischemic area. Reperfusion may cause additional tissue stress, sometimes worsening damage.
Current strategies to protect tissues from the effects of ischemic and reperfusion damage are limited. The primary approach involves the delivery of drugs for prevention, such as anti-platelet agents (e.g. aspirin, abciximab), anti-coagulants (e.g. warfarin, tissue plasminogen activator (tPA)), anti-inflammatory agents (e.g. aspirin), diuretics (e.g. furosemide), vasodilators (e.g. nitroglycerine, ACE inhibitors), and anti-hypertensive medications (e.g. atenolol). Such drugs reduce the causative factors involved in arterial blockage; however, they do not provide protection to a tissue affected by an ischemic event. In addition, not all patients benefit from these treatments, due in part to factors including drug insensitivity, drug toxicities, and other risks (e.g. hemorrhage), and drug interactions.
In addition to drug-based strategies, approaches have been developed to diminish the injury associated with an acute ischemic event. Such techniques focus on restoring blood flow by use of angioplasty, arterial stenting, coronary bypass, and treatment with thrombolytic drugs (e.g. tPA). These treatments may improve patient prognosis, however, tissue damage can occur from the procedure including the acute risk of vessel rupture and ischemic damage, and delayed risks include restenosis, or reocclusion of the occluded vessel leading to additional ischemic events. For example, following arterial stenting procedures, restenosis occurs in 10-40% of cases (van der Hoeven, B. L. et al., Int J. Cardiol., 99(1):9 2005).
There a need for a treatment method for reducing tissue damage in an ischemic and reperfusion events. In addition, there exists a need for nanodevices for the treatment of patients, including patients in which current pharmaceutical solutions are unacceptable.